Methyl chloroformate → HCID 71515726, compound

HRID 574646Notes

Reaction equation

C([N:4]1[CH2:9][CH2:8][C:7]2[N:10]([C@@H:21]3[C:29]4[C:24](=[C:25]([F:31])[CH:26]=[C:27]([F:30])[CH:28]=4)[CH2:23][C@H:22]3[OH:32])[N:11]=[C:12]([C:13]3[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=3)[C:16]#[N:17])[C:6]=2[CH2:5]1)(=O)C.Cl[C:34]([O:36][CH3:37])=[O:35].CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:37][O:36][C:34]([N:4]1[CH2:9][CH2:8][C:7]2[N:10]([C@@H:21]3[C:29]4[C:24](=[C:25]([F:31])[CH:26]=[C:27]([F:30])[CH:28]=4)[CH2:23][C@H:22]3[OH:32])[N:11]=[C:12]([C:13]3[CH:20]=[CH:19][CH:18]=[C:15]([C:16]#[N:17])[CH:14]=3)[C:6]=2[CH2:5]1)=[O:35]

Participants

Conditions

Temperature: 2.5 °C

Procedure

According to Scheme 11: To a solution of 3-[1-((1R,2R)-4,6-difluoro-2-hydroxy-indan-1-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (11t) (0.05 g, 0.123 mmol) in dry CH2Cl2 (2 ml) at 0° C. methyl chloroformate (12 mg, 0.13 mmol) and NEt3 (19 mg, 0.191 mmol) was added, the mixture was stirred at 0-5° C. for 60 min, then at 25° C. for 18 h. After addition of aqueous saturated NaHCO3 (2 ml), the mixture was extracted with CH2Cl2 (10 ml), the organic layer was dried over Na2SO4, solvents were evaporated in vacuo and the crude product was purified by purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 31 mg of 3-(3-cyano-phenyl)-1-((1R,2R)-4,6-difluoro-2-hydroxy-indan-1-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methyl ester (17a).

Workup

waitat 25° C. for 18 h
extractionthe mixture was extracted with CH2Cl2 (10 ml)
dry with materialthe organic layer was dried over Na2SO4, solvents
customwere evaporated in vacuo
customthe crude product was purified
customby purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-c87844c08d9c4e1a92c641f32cb6387f
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034897B2

Reaction notes

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